In recent years, the use of plastic, disposable pipette tips has expanded rapidly. In biotechnology and medical research, such as polymerase chain reactions (PCR), tissue culture, serological assays, forensic assays, nucleic acid or protein loadings and pipetting of radioactive samples, there are now literally hundreds of millions of these tips used in the United States each year. Typically, the plastic tips are used with pipetters, and in most applications each tip is used once and then disposed of so as to avoid contamination and eliminate the need for cleaning of the tips. Thus, a single pipetter will be used with hundreds and even thousands of disposable tips in the course of a week.
Although disposal of these tips has substantially reduced cross-contamination of samples, this problem still occurs, most commonly caused by carry over from one test tube to another. Another cause of contamination, however, is due to exposure of the pipetter barrel and shaft of conventional air-displacement micropipetters with aerosols generated during aspiration of fluid samples into and out of the disposable pipette tips. In certain situations, such as in PCR, which provides a method to produce multiple copies of a specific nucleotide sequence from small quantities of DNA, the reactions are so sensitive that even a minute exposure may be critical. Hours or even days of laboratory research may be wasted due to this contamination.
Yet another form of contamination of the pipetter barrel may be caused by fluid absorption from substances such as amplified DNA, radioisotopes, or infectious materials due to actual contact of the sample therewith. Contact with the fluid is often caused by uncalibrated pipetters or shoddy technique, such as overdraw and tipping of the pipetter, or mishandling which causes splashing during the drawing phase of pipetting.
To overcome these problems, positive displacement pipetters have been employed to reduce cross-contamination of samples caused by aerosol contamination of the pipetter barrel. These pipetters, however, are limited in use due to their cost, complexity, and time consumption during applications, especially when multiple pipetting is necessary.
Another attempt to eliminate aerosol and fluid sample contact contamination of the pipetter barrel involves wedging a relatively thick filter membrane into a receiving chamber defined by the dispensable pipette tip. The filter forms an aerosol and liquid interactive sealing barrier between the drawn fluid and the pipetter barrel. Typical of this invention is the device disclosed in U.S. Pat. No. 5,156,811.
While this arrangement has been effective to reduce aerosol contamination of the pipetter barrel, several problems are inherent with these designs. For instance, each filter must be individually positioned inside each pipetter tip which is an enormous and laborious undertaking, especially with the standard 8.times.12 array micro-titer plates (i.e., 96 tip racks) employed during manufacture. Further, since the filter membranes are frictionally secured by pushing them down into the receiving chamber, critical storage and dispensing capacity are reduced by the filter membrane. Hence, the full volumetric capabilities of the pipette tips having filters mounted therein are not realized. Upon contact of the filter with the sample fluid, these pipette tips require immediate replacement since a sealing gel barrier is formed in the filter which is liquid and gas impenetrable. Moreover, the relatively thick filter membrane adds resistance to fluid drawing and dispensing, which may reduce pipetting accuracy.